Home > Groups > Baoyang HU

Baoyang HU, Ph. D.

Human stem cells, neural differentiation and regeneration


Co-workers: Yihui Wu, Dongmei Wang, Da Zhang, Guilai Chen, Menghua Wu, Dewen Ding, Yi Wang, Wenliang Zhu, Yaming Yang, Longkuo Xia

• HU Group website

 

  We are trying to understand mechanisms of human neural differentiation, and dedicate to translating our research into stem cell based therapy and regenerative medicine.
  We have devised a chemically defined culture system, with which we can convert human ESCs or iPSCs to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. Based upon our expertise in neural differentiation of human PSCs, we’ll investigate how cell signaling and epigenetic program coordinate the transcription factors to convert human PSCs toward certain type of neurons or glia. An understanding of this knowledge will allow us to develop protocols for scalable production of functional human cells, either through directed differentiation from PSCs or by direct conversion of other types of somatic cells. We’ll use mammalian and non-human primate models of the relevant neurological diseases, such as Parkinson disease, Huntington disease and stroke, to investigate how the graft cells integrate into the native circuits of the host brains. Concurrently, using a lately developed protocol of cerebral organoid culture from hPSCs, we are able to discover the unique elements that determine the advanced features of human brain, such as the enlarged cortex and increased gyri. This would allow us to explore in depth the developmental regulation that happens only in human, but not in animal models. .



Reactive astrocytes are temporally heterogeneous and affect the integration of transplanted neural cells.



Overexpression of Mash1 convert astrocytes to projection striatal GABAergic neurons (medium spiny neurons, MSNs).



Cerebral organoids generated from hESCs in 3D culture.(Green: CTIP2, Red: SOX2, Blue: Hoechst).

 

Plain English:
  Human pluripotent stem cells (PSC), including embryonic stem cells (ESCs) from the earliest embryo and induced pluripotent stem cells (iPSCs) reprogrammed from the somatic cells, hold great promise in regenerative medicine because of their high potential to differentiate into virtually any cell type in the body. We devised a chemically defined culture system, in which the human PSCs were able to differentiate into functionally specialized neurons and glia that hold the native regional identity of the central nervous system. We’ll continue to use this system to dissect the regulatory mechanisms that direct human PSCs differentiating into functional neural cells, and further refine our protocols for scalable production of functional cells. We are also planning to investigate how the graft neurons integrate into the native circuits of the brain, especially under the diseased condition. This knowledge will help us to develop the stem cell based therapeutic strategies for those currently incurable neural degenerative diseases as well as brain and spinal cord injuries.

 

Selected publications:

  1.  Li Z, Wan H, Feng G, Wang L, He Z, Wang Y, Wang X, Li W, Zhou Q, Hu B. Birth of fertile bimaternal offspring following intracytoplasmic injection of parthenogenetic haploid embryonic stem cells. Cell research 26(2016), 135-138.
  2. Jiang Y, Du M, Wu M, Zhu Y, Zhao X, Cao X, Li X, Long P, Li W, Hu B. Phosphatidic Acid Improves Reprogramming to Pluripotency by Reducing Apoptosis. Stem cells and development 25(2016), 43-54.
  3. Zhu H, Tan Y, Gu Q, Han W, Li Z, Meyer J, Hu B. Regulations in the United States for cell transplantation clinical trials in neurological diseases. Translational Neuroscience and Clinics. 1(2015), 114-124.
  4. Wang S, Li W, Wang S, Hu B. Rapid and efficient assembly of transcription activator-like effector genes by USER cloning. Journal of genetics and genomics 41(2014), 339-347.
  5. Wu M, Chen G, Hu B. Induced pluripotency for translational research. Genomics, proteomics & bioinformatics(2013)11, 288-293.
  6. Jiang Y, Zhang M, Hu B. Specification of functional neurons and glia from human pluripotent stem cells. Protein & cell 3(2012), 818-825.
  7. Ma L, Hu B, Liu Y, Vermilyea S, Liu H, Gao L, Sun Y, Zhang X, Zhang S. Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice. Cell stem cell 10(2012), 455-464.
  8. Hu B, Weick J, Yu J, Ma L, Zhang X, Thomson J, Zhang S. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency.  PNAS 107(2010), 4335-4340.
  9. Hu B, Du Z, Li X, Ayala M, Zhang S. Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136(2009a), 1443-1452.
  10. Hu B, Zhang S. Differentiation of spinal motor neurons from pluripotent human stem cells. Nature protocols 4(2009), 1295-1304.
  11. Hu B, Du Z, Zhang S. Differentiation of human oligodendrocytes from pluripotent stem cells. Nature protocols 4(2009), 1614-1622.